Cardioprotective Effect of Gedunin on Isoproterenol-Induced Cardiotoxicity through the Attenuation of NF-κB-Mediated Inflammatory Pathway in Rats

Background: There is an increasing interest in new natural compounds for the treatment of myocardial infarction (MI). Gedunin is a tetranortriterpenoid extracted from the Indian neem tree (Azadirachta indica). The main objective of this study is to understand the cardioprotective effects of gedunin against MI through the suppression of NF-kappa B-mediated inflammatory pathways. Materials and Methods: Male Wistar rats were categorized into 4 groups of 6 each: control, inducer isoproterenol (ISO) alone, ISO + gedunin-treated, and gedunin (50 mg/kg b.w.)-pretreated rats followed by ISO induction. The infarct size, heart-to-body weight ratio, cardiac enzymes, ATP values, Ca2+ levels, and inflammatory and apoptotic markers were studied and compared in all these groups. Data were expressed as mean +/- SD. One-way analysis of variance (ANOVA) and post hoc Tukey-Kramer test were used for comparing multiple values. Results: Gedunin pre-treatment caused a reduction in cardiac size, attenuated the levels of cardiac bio-enzymes, and reduced immune cell infiltration and necrosis. It also enhanced the secretion of antioxidant enzymes glutathione-S-transferase (GST) and superoxide dismutase (SOD) and reduced glutathione (GSH) and glutathione peroxidase (GPx). Gedunin suppressed inflammation by down-regulating the secretion of interleukin 10 (IL-10), interleukin-1 beta (IL-1 beta), nuclear factor-kappa B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha), and apoptotic markers caspase-3, caspase-9, Bax, and Bcl-2. Conclusion: Gedunin inhibited apoptosis in cardiotoxicity-induced MI in rats by inhibiting inflammation and apoptosis markers. Thus, gedunin is a potential natural cardioprotective compound.